Maria Fornal

Association of red blood cell distribution width, inflammation markers and morphological as well as rheological erythrocyte parameters with target organ damage in hypertension

OBJECTIVES To assess the relationships of red blood cell distribution width (RDW), mean corpuscular hemoglobin concentration (MCHC) and erythrocyte deformability with pathological changes of selected target organs, and with inflammation markers interleukin-6 (IL-6) and fibrinogen, in a group of newly diagnosed, never-treated and otherwise healthy hypertensive patients. METHODS The study group consisted of 101 adults divided into three sub-groups: 37 diagnosed arterial hypertension, 29 with hypercholesterolemia, and 35 healthy. The individuals with hypertension or hypercholesterolemia were otherwise healthy and were not on any therapy prior to entering the study. For each individual, data were obtained on: systolic and diastolic blood pressure (SBP, DBP), pulse wave velocity (PWV), carotid intima media thickness (IMT), left ventricle geometry, blood morphology, lipids profile, fibrinogen, CRP, IL-6 and red blood cell deformability index (DI). RESULTS In the group of hypertensives, the multivariate regression analysis showed significant relationship of RDW with PWV, IL6 and fibrinogen. Also, RDW was found to be correlated with MCHC and DI, and MCHC was significantly related to IMT and IL-6. CONCLUSIONS A hypothesis has been formulated that the development of target organ damage in hypertension is accompanied by the increasing impairment of erythropoiesis. This process may be mediated by inflammation.

Rheological properties of erythrocytes in patients with high risk of cardiovascular disease

Rheological properties of erythrocytes from patients with high risk of cardiovascular disease (CVD) were analyzed in relation to individual patient risk factors as well as to the medication. Additionally, comparative statistical analysis was performed considering plasma concentration of the selected mediators of vascular endothelium: 6-keto-prostaglandin F(1alpha) (PGF(1alpha)), sVCAM-1 and E-selectin adhesion molecules and interleukin-6 (IL-6). It was found that antihypertensive therapy with angiotensin-converting enzyme inhibitor (ACEI) is accompanied by improvement of RBC rheology: the increase of deformability and the decrease of aggregability. This improvement is probably mediated by endothelial prostacyclin and nitric oxide which are generated by ACEI. A correlation was observed between RBC deformability/aggregability and the patients hematocrit level, what implicates that the hematocrit level should be explicitly taken into consideration when investigating rheological properties of erythrocytes. A strong relationship was also found between the plasma concentration of sVCAM-1 and patients age.

Left ventricular geometry and rheological properties of erythrocytes in patients at cardiovascular disease risk.

The relationship between erythrocyte deformability and aggregability with left ventricular mass index has been examined in patients diagnosed with at least one cardiovascular risk factor but without ongoing coronary heart disease. The group consisted of 66 individuals, 30 men and 36 women, of the average age 57.7 years. For each patient, deformability and aggregability of red blood cells (RBCs) as well as end-diastolic left ventricle diameter (LVD), interventricular septum thickness (IVST) and posterior wall thickness (PWT) were measured. On the basis of the echocardiographical parameters and anthropometric data, left ventricular mass index (LVMI) was calculated. The analysis revealed statistically significant correlation between the LVMI and erythrocyte deformability and aggregability: the LVMI increases with decreasing deformability and is higher in patients with higher aggregability. This finding indicates that the worsening of RBC rheological properties is one of the main factors contributing to alterations of cardiac geometry through the increase of peripheral resistance which, in turn, significantly augments the heart afterload. Given that left ventricular hypertrophy (LVH) is a predictor of cardiovascular morbidity and mortality, the association between hemorheological parameters and left ventricular geometry may be important in clinical practice.

Relevance of erythrocyte deformability to the concentration of soluble cell adhesion molecules and glomerular filtration rate in patients with untreated essential hypertension

Relationship between erythrocyte deformability and: a) soluble cell adhesion molecules concentration, b) glomerular filtration rate (eGFR) has been investigated in three study groups: a group of 20 patients with diagnosed arterial hypertension, a group of 20 individuals with exclusively hypercholesterolemia and a group of 22 healthy persons. The individuals with hypertension or hypercholesterolemia were free of any other cardiovascular disease risk factor and were not on any therapy prior to entering the study. Clinical and laboratory data included systolic and diastolic blood pressure (obtained by ABPM), lipids profile, eGFR, red blood cell (RBC) deformability (assessed by shear stress laser diffractometry) and levels of circulating soluble vascular adhesion molecules-1 (sVCAM-1) as well as soluble intracellular adhesion molecules-1 (sICAM-1). In the group of hypertensives, RBC deformability and concentration of circulating soluble adhesion molecules showed statistically significant negative correlations: RBC deformability decreases with increasing level of: a) sVCAM-1, R = -0.61, p < 0.002, b) sIVCAM-1, R = -0.53, p < 0.009. In parallel, statistically significant increase of eGFR was observed with rising erythrocyte deformability, R = 0.60, p < 0.005. In the groups of healthy individuals and patients with hypercholesterolemia there was no sign of any correlations between the considered parameters. The observed correlations suggest that in patients diagnosed exclusively with hypertension, firstly, erythrocyte deformability may serve as a marker of endothelial dysfunction and, secondly, red blood cells may be mediators of adverse changes in kidneys.

Evolution of rheological properties of erythrocytes and left ventricular geometry in cardiovascular disease risk patients.

The evolution of rheological properties of erythrocytes and geometrical parameters of left ventricle during therapies aimed at reducing cardiovascular disease (CVD) risk has been investigated. The study group consisted of 29 individuals who were diagnosed with the presence of at least one CVD risk factor at the time of entry to the study. Appropriate therapies were applied and the patients were followed for two years. Two groups of patients could be distinguished. The first group consisted of 12 individuals who were rigorously applying the therapy and for whom blood pressure, total cholesterol, LDL and glucose returned to normal levels. The second group included 17 patients for whom the above mentioned parameters remained pathological in spite of the applied therapy. In the first group, erythrocyte deformability as well as LVMI improved: deformability increased on average by 17% (p < 0.025), whereas LVMI decreased by 8% but not in a statistically significant manner (p < 0.27). In the second group, the results indicate worsening of both hemorheological properties and left ventricular geometry: RBC deformability became lower by 15% (p < 0.00001) and LVMI increased by 18% although this change was not statistically significant (p < 0.19). The results indicate that blood rheology improves when the CVD risk is reduced by administered therapy and worsens when the risk increases. Similar behavior shows LVMI. It is very likely that left ventricular geometry is influenced by blood rheology.

Women with prehypertension in primary care - Risk profile on the basis of selected cardiovascular risk factors.

Abstract Background. Demographic, social and economic trends will serve to increase the importance of women as healthcare consumers. Design. The aim of the study was to assess cardiovascular (CV) risk in the normotensive female patients during single visit to primary care (PC) offices. Methods. Demographic data, history of coronary heart disease (CHD), diabetes (DM), smoking habit and family history of CV diseases were obtained from women who visited general practitioners. Moreover, blood pressure (BP), pulse rate, weight and height used to calculation body mass index (BMI) and waist circumference (WC) were performed. Prehypertension was defined as a systolic BP (SBP) of 120–139 mmHg, and/or a diastolic BP (DBP) of 80–89mmHg. Results. Prehypertension was observed in 21.5% of the whole group of female PC patients. SBP, DBP, BMI and WC revealed significant trends towards increase with age among both prehypertensives (p<0.001) and normotensives (SBP, BMI, WC: p<0.001; DBP: p<0.05) and in the whole group (p<0.001). Nevertheless, heart rate (HR) significantly increased with age only among prehypertensive women (p<0.05). The CV risk of the studied adult women increased progressively with presence of overweight, obesity and visceral obesity. The CV risk of the youngest groups was associated mainly with high prevalence of smoking, and with high prevalence of CHD and DM among the oldest female patients. Conclusions. The prevalence of majority of CV risk factors increase with age among both prehypertensive and normotensive women, which should stimulate PC practitioners to identify and modify them.

The influence of very small doses of alpha radiation on the stability of erythrocytes

Our aim was to study the influence of low doses (0.2–4 μGy) of α radiation on the stability of human erythrocytes isolated from healthy and diabetic erythrocytes. Absorption spectroscopy was used to measure the level of red blood cell (RBC) hemolysis, along with Mössbauer spectroscopy, which is a highly specific method suited to monitoring various hemoglobin forms. States of hemoglobin are sensitive to a homeostatic imbalance in red blood cells. Changes in the membrane skeleton organization of irradiated erythrocytes isolated from healthy donors were studied using atomic force microscopy (AFM). Hemolysis, in healthy red blood cells, showed characteristic discontinuities, depending on the α particle flux and the exposure time to the low doses applied. This phenomenon was not observed in severe diabetic cases, which could be a result of modified protein–lipid–sugar complexes and the attenuation/absence of some antioxidative enzymatic processes in their RBC membranes. Similar effects were also observed for red blood cells treated with low doses of neutron and γ‐radiation. AFM measurements demonstrated a reorganization of the RBC membrane skeleton network depending on the time of RBC exposure to α radiation. This suggests that the changes in the activity of the acute defense processes against free radicals which are activated within the erythrocyte membrane irradiated with α‐particles could additionally be up‐ or down regulated by modifications to the membrane–skeleton network. However, even the highest dose of α radiation applied in these studies did not cause any significant changes in the ability of hemoglobin to transport oxygen. Microsc. Res. Tech. 80:131–143, 2017.

Multifractal characterization of morphology of human red blood cells membrane skeleton.

The purpose of this paper is to show applicability of multifractal analysis in investigations of the morphological changes of ultra‐structures of red blood cells (RBCs) membrane skeleton measured using atomic force microscopy (AFM). Human RBCs obtained from healthy and hypertensive donors as well as healthy erythrocytes irradiated with neutrons (45 μGy) were studied. The membrane skeleton of the cells was imaged using AFM in a contact mode. Morphological characterization of the three‐dimensional RBC surfaces was realized by a multifractal method. The nanometre scale study of human RBCs surface morphology revealed a multifractal geometry. The generalized dimensions Dq and the singularity spectrum f(α) provided quantitative values that characterize the local scale properties of their membrane skeleton organization. Surface characterization was made using areal ISO 25178‐2: 2012 topography parameters in combination with AFM topography measurement. The surface structure of human RBCs is complex with hierarchical substructures resulting from the organization of the erythrocyte membrane skeleton. The analysed AFM images confirm a multifractal nature of the surface that could be useful in histology to quantify human RBC architectural changes associated with different disease states. In case of very precise measurements when the red cell surface is not wrinkled even very fine differences can be uncovered as was shown for the erythrocytes treated with a very low dose of ionizing radiation.

Erythrocyte heme‑oxygenation status indicated as a risk factor in prehypertension by Raman spectroscopy

Raman spectroscopy of erythrocytes provides detailed information about the structure and status of heme moiety, which can be used to provide new insights into molecular pathogenesis of several diseases. In this study, we present the first Raman spectroscopy investigations of the effect of hemoglobin oxygenation in the context of hypertensive disease. The experimental data was subjected to Logistic Regression, which indicated heme‑oxygenation status as an important risk factor alongside other clinical parameters. The 1605/1621 cm-1 band ratio was selected as an optimal Raman metric for risk assessment and along with other band ratios (1583, 1639, 1310 cm-1) related to heme status and when combined with clinical data via logistic regression gave an Area Under the Curve (AUC) >0.95 for prehypertension risk prediction. The work demonstrates the feasibility of Raman spectroscopy to distinguish between prehypertensive and normotensive states. Simultaneously, it is implied that the etiology of the high blood pressure progression may be connected with the changes in hemoglobin oxygenation.